Abstract The AIDS epidemic, initially recognized in the early 1980's, currently affects more than 35 million people worldwide. Infection with the human immunodeficiency virus (HIV) is associated with a wide range of long term health complications including the development of cancer, currently a major cause of death among persons living with HIV/AIDS. The early form of the AIDS and Cancer Specimen Resource (ACSR) was established in 1994 as a cooperative agreement with the NCI with a mission to provide high quality biospecimens to researchers, a mission still paramount for the current ACSR. Principle investigators (MPIs) from the two legacy sites (GWU and UCSF) oversee the function of the ACSR to ensure the adherence to NCI best practices in this multinational program. The ACSR is currently the custodian for specimen collections from more than 20,000 individuals and makes these biospecimens available to eligible researchers studying HIV and cancer through an established specimen application process. In the past five years, investigators from more than 50 institutions have received research material from the ACSR. In addition, the ACSR has provided the centralized biospecimen collection and distribution functions for the AIDS Malignancy Consortium (AMC), which represents the NCI-funded international network of more than 30 clinical institutions involved in testing novel cancer therapies in HIV-infected individuals. The ACSR is structured into regional biospecimen repositories (RBRs) located in distinct geographical regions that reflect the US and global HIV epidemic and are unified (virtually) by an informatics infrastructure managed by the Hub for Integrated Informatics and Research Support (HIIRS). The RBRs are distinct but complementary in their diverse functions, with collaborative interactions fostered through the Governing Committee and ACSR-wide Working Groups that accomplish activities related to Science and Technology, Marketing and Outreach, Informatics, and Quality Management. As the HIV epidemic has evolved the types of cancers and the technologies used to study them have also changed. The newly reconfigured ACSR will have two divisions, both focused on obtaining the most important well-annotated (demographic, clinical, pathological and outcomes data) biospecimens for research as defined by investigator inquiries and the ACSR's scientific advisory board. The two MPIs, respectively will head the national and international AMC support program and the scientific direction of the ACSR. Both MPIs will work within the structure of the ACSR to obtain and provide to researcher's specimens most important for research in the current epidemic. Specific Aims include: 1) Acquire, store, and equitably distribute tumor tissues and biological fluids from individuals with HIV-associated malignancies (AIDS-defining cancers and non-AIDS defining cancers) to meet the biospecimen needs of researchers in HIV-associated malignancies; and 2) Promote the success of AMC clinical trials through mutually beneficial collaborations.